Olinkage to GalNAc

1
Posttranslation Modifications 1
Vitamin K-Dependent Modifications Vitamin K
is a cofactor in the carboxylation of glutamine
residues. The result of this type of reaction is
a g-carboxyglutamate (called a gla residue). The
formation of gla residues within several proteins
of the blood clotting cascade is critical for
their normal function. The presence of gla
residues allows the protein to chelate calcium
ions and thereby render an altered conformation
and biological activity to the protein.
O-linkage to GalNAc
N-linkage to GlcNAc
2
Posttranslation Modifications 2
Sulfation Sulfate modification of proteins
occurs at tyrosine residues such as in fibrinogen
and in some secreted proteins (eg gastrin). The
universal sulfate donor is 3'-phosphoadenosyl-5'-p
hosphosulphate (PAPS). Since sulfate is
added permanently it is necessary for the
biological activity and not used as a regulatory
modification like that of tyrosine
phosphorylation.
Selenium is a trace element and is found as a
component of several prokaryotic and eukaryotic
enzymes that are involved in redox reactions. The
selenium in these selenoproteins is incorporated
as a unique amino acid, selenocysteine, during
translation. A particularly important eukaryotic
selenoenzyme is glutathione peroxidase. This
enzyme is required during the oxidation of
glutathione by hydrogen peroxide (H2O2) and
organic hydroperoxides.
3

Phosphorylation Post-translational
phosphorylation is one of the most common protein
modifications that occurs in animal cells. The
vast majority of phosphorylations occur as a
mechanism to regulate the biological activity of
a protein and as such are transient. In other
words a phosphate (or more than one in many
cases) is added and later removed. The
enzymes that phosphorylate proteins are termed
kinases and those that remove phosphates are
termed phosphatases.
ATP protein lt----gt phosphoprotein ADP
4
In animal cells serine, threonine and tyrosine
are the amino acids subject to phosphorylation.
The largest group of kinases are those that
phsophorylate either serines or threonines and as
such are termed serine/threonine kinases. The
ratio of phosphorylation of the three different
amino acids is approximately 1000/100/1 for
serine/threonine/tyrosine. Although the level of
tyrosine phosphorylation is minor, the importance
of phosphorylation of this amino acid is
profound. As an example, the activity of numerous
growth factor receptors is controlled by tyrosine
phosphorylation.